ArticleWorld journal of gastrointestinal pharmacology and therapeutics2010
Z α-1 antitrypsin deficiency and the endoplasmic reticulum stress response.
Article in World journal of gastrointestinal pharmacology and therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Rare variants in alpha 1 antitrypsin deficiency: a systematic literature review.Orphanet journal of rare diseases · 2024Pooled it
- Alpha-1 antitrypsin deficiency: genetics, clinical manifestations, AI prognostics, and advanced imaging in liver disease.Annals of medicine and surgery (2012) · 2025Review
- Mendelian causes of early-onset emphysema: a review of the current literature.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Quantitative Proteomic Analysis of Non-Tobacco Associated Oral Squamous Cell Carcinoma Reveals Deregulation of Cytoskeletal and Apoptotic Proteins.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- The unfolded protein response to PI*Z alpha-1 antitrypsin in human hepatocellular and murine models.Hepatology communications · 2022Article
- Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.Bioengineering (Basel, Switzerland) · 2022Review
- Alu RNA induces NLRP3 expression through TLR7 activation in α-1-antitrypsin-deficient macrophages.JCI insight · 2022Article
- The Mechanism of Mitochondrial Injury in Alpha-1 Antitrypsin Deficiency Mediated Liver Disease.International journal of molecular sciences · 2021Article
- Protein Misfolding and Aggregation: The Relatedness between Parkinson's Disease and Hepatic Endoplasmic Reticulum Storage Disorders.International journal of molecular sciences · 2021Review
- Roles of XBP1s in Transcriptional Regulation of Target Genes.Biomedicines · 2021Review
- Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis.International journal of molecular sciences · 2021Review
- The Probable, Possible, and Novel Functions of ERp29.Frontiers in physiology · 2020Article
- Calcium signalling in mammalian cell lines expressing wild type and mutant human α1-Antitrypsin.Scientific reports · 2019Article
- Control of Protein Homeostasis in the Early Secretory Pathway: Current Status and Challenges.Cells · 2019Review
- Modulation of calreticulin expression reveals a novel exosome-mediated mechanism of Z variant αThe Journal of biological chemistry · 2019Article
- Cell death and cell death responses in liver disease: mechanisms and clinical relevance.Gastroenterology · 2014Review
- The role of bronchial epithelial cells in the pathogenesis of COPD in Z-alpha-1 antitrypsin deficiency.Respiratory research · 2014Article
- Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding.Toxicology and applied pharmacology · 2014Article
- The unfolded protein response in fatty liver disease.Seminars in liver disease · 2013Review
- Alcoholic lung injury: metabolic, biochemical and immunological aspects.Toxicology letters · 2013Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serine proteinase inhibitor α-1 antitrypsin (AAT) is produced principally by the liver at the rate of 2 g/d. It is secreted into the circulation and provides an antiprotease protective screen throughout the body but most importantly in the lung, where it can neutralise the activity of the serine protease neutrophil elastase. Mutations leading to deficiency in AAT are associated with liver and lung disease. The most notable is the Z AAT mutation, which encodes a misfolded variant of the AAT protein in which the glutamic acid at position 342 is replaced by a lysine. More than 95% of all individuals with AAT deficiency carry at least one Z allele. ZAAT protein is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum (ER) of hepatocytes and other AAT-producing cells. This results in a loss of function associated with decreased circulating and intrapulmonary levels of AAT. However, the misfolded protein acquires a toxic gain of function that impacts on the ER. A major function of the ER is to ensure correct protein folding. ZAAT interferes with this function and promotes ER stress responses and inflammation. Here the signalling pathways activated during ER stress in response to accumulation of ZAAT are described and therapeutic strategies that can potentially relieve ER stress are discussed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.